This R21 application is a Phase II clinical trial exploring the efficacy of modafinil as a smoking cessation aid. It builds on a Phase I Clinical Trial (R03) that explored the safety of modafinil in combination with nicotine and the effects of modafinil on nicotine withdrawal. Modafinil administration was safe, decreased appetite and cigarette craving, and enhanced attention after 24 hrs of tobacco deprivation in tobacco smokers. This proposal is responding to the RFA: "Women, Gender Differences and Drug Abuse" in that it is developing and testing a theoretically-based drug treatment that addresses a gender-specific issue. It addresses the observation that weight gain following smoking cessation is a significant deterrent to treatment efficacy among women. Further, the application is consistent with the goals of the R21 mechanism in that it is testing a novel intervention with significant potential to have a major impact on smoking cessation among women. Although the mainstays of pharmacological interventions for smoking cessation, bupropion and nicotine replacement, can double smoking cessation rates, the majority of smokers continue to smoke, especially women. Cigarette smoking is the leading cause of preventable death and disease and may have greater health risks for females than males, so exploration of novel pharmacological interventions is imperative. Modafinil has particular promise as a smoking cessation aid in that it has the potential to ameliorate multiple symptoms of nicotine withdrawal, including 1) craving, 2) inattention, 3) depressed mood and 4) increased appetite and weight gain. This Phase II clinical trial will be a randomized, double blind, placebo-controlled smoking cessation intervention that will compare the efficacy of 200 mg of modafinil and placebo on smoking cessation. In addition, modafinil effects on nicotine withdrawal symptoms will be assessed, including craving, inattention, depressed mood and increased appetite and weight gain in nicotine-dependent smokers undergoing smoking cessation treatment. Finally, personality measures that evaluate depressed mood and inattention will be obtained since these variables have been associated with increased risk for cigarette smoking. This combination of measures of smoking cessation, nicotine withdrawal symptoms and personality measures that are associated with risk for smoking will aid in evaluating whether modafinil is a smoking cessation aid and will also allow examination of possible mechanisms for the effects of modafinil on smoking cessation. If shown to be effective, modafinil could be added to the current pharmacotherapies for smoking cessation and may have particular benefit for female smokers for whom weight gain is a significant deterrent to smoking cessation. Most smokers trying to quit often fail because of increased cigarette craving, inattention, appetite, and weight. We have shown that the medication, modafinil, decreases appetite and cigarette craving and improves concentration when smokers first stop smoking. This suggests that modafinil will help smokers stop smoking by decreasing appetite and craving and increasing concentration. Modafinil may be particularly helpful for women smokers who have concerns about weight since modafinil decreases appetite when smokers are in nicotine withdrawal. [unreadable] [unreadable] [unreadable]